The American Cancer Society estimates that 48,330 new cases of cancer in the oral cavity and pharynx will be reported this year. When diagnosed at early stages, the 5-year survival rate is 83%. However, when diagnosed at intermediate or advance stages, the 5-year survival rate drops to 62% and 38%, respectively. In addition, while early stage treatment may only require minor surgery to remove the localized tumor, later stage treatment could require surgical removal of parts of the face and neck, hence drastically reducing the patient?s quality of life. Unfortunately, benign oral lesions are sometimes difficult to distinguish from dysplasia or early invasive cancer even for healthcare professionals. As a result, only 31% of patients are diagnosed at early stages despite the fact that the oral cavity is easily accessible for direct examination. Hence, there is a critical need for new clinical technologies for reliable early diagnosis of oral cancer and dysplasia. Several screening tools for oral cancer have been commercially available, including exfoliative cytology, vital staining, salivary test, and optical interrogation; however, none of them have been demonstrated to be capable of clinically relevant sensitivity and specificity. We hypothesize that several biomarkers for oral cancer and dysplasia can be accurately quantified by endogenous fluorescence lifetime imaging (FLIM) thus enabling levels of sensitivity and specificity adequate for early detection. This bioengineering research grant focuses on developing and validating a cost-effective wide-field multispectral FLIM endoscope for noninvasive in situ detection of oral cancer and dysplasia. To that end we have developed three specific aims. Aim 1: To design and build a cost-effective multispectral FLIM endoscope for in vivo imaging of epithelial tissue in the oral cavity. Aim 2: To develop algorithms for fast and automated FLIM based early detection of oral epithelial cancer and dysplasia. Aim 3: To quantify prospectively in a pilot clinical study the capability of the proposed FLIM endoscopic tools for noninvasively early detection of oral epithelial cancer and dysplasia. The successful completion of these aims will result in a novel, accurate and cost-effective clinical tool for noninvasive in situ early detection of cancer and dysplasia. Such a tool could potentially help to improve significantly both the life expectancy and the quality of life for the more than 33,000 oral cancer patients being diagnosed each year at intermediate and advance stages. Beyond early diagnosis, this tool could also assist at every step involved on the clinical management of oral cancer patients, including treatment guidance and monitoring of disease recurrence. Finally, the demonstrated success of this clinical tool in oral epithelial cancer will herald future success with other cancers of epithelial origin, which accounts for more than 80% of all cancers.